Rezoklastin concentrate, vial 5mg/6.25ml

Composition

1 bottle contains 6.25 ml (5 mg zoledronic acid) of concentrate.

Pharmacological action

Rezoklastin belongs to a new class of highly effective bisphosphonates that have a selective effect on bone tissue. Zoledronic acid suppresses the activity of osteoclasts, does not have an undesirable effect on the formation, mineralization and mechanical properties of bone tissue.

The selective effect of bisphosphonates on bone tissue is based on a high affinity for mineralized bone tissue, but the exact molecular mechanism that provides inhibition of osteoclast activity is still unclear. Zoledronic acid, in addition to its inhibitory effect on bone resorption, has direct antitumor properties that provide effectiveness in bone metastases.

In vitro, it was found that zoledronic acid suppresses cell proliferation and induces apoptosis, has a direct antitumor effect on myeloma and breast cancer cells, and reduces the risk of their metastasis. Inhibition of osteoclastic bone resorption leads to a decrease in the growth of tumor cells; antiangiogenic and analgesic activity is noted. Zoledronic acid also inhibits the proliferation of human endothelial cells. When hypercalcemia is caused by a tumor, it reduces the concentration of calcium in the blood serum.

When using zoledronic acid in patients with postmenopausal osteoporosis (values of the T-criterion of bone mineral density of the femoral neck less than -2.5), there was a statistically significant reduction in the risk of vertebral fractures, as well as a decrease in the risk of developing one or more new (repeated) vertebral fractures.

When treated with zoledronic acid in patients with Paget’s bone disease, a statistically significant, rapid and long-term therapeutic response was observed, as well as normalization of the level of bone metabolism and ALP concentration in blood plasma.

The drug is also highly effective in patients who have previously received treatment with oral bisphosphonates. It was found that the majority of patients treated with zoledronic acid have a therapeutic response that persists throughout the entire treatment period (about 2 years).

In patients with postmenopausal osteoporosis and Paget’s bone disease, zoledronic acid does not affect the quality of normal bone, does not interfere with the processes of bone remodeling and mineralization, and contributes to the preservation of normal trabecular bone architectonics.

Indications

• Hypercalcemia (serum albumin-adjusted calcium concentration >12 mg/dl or 3 mmol/L) induced by malignant tumors.
• Postmenopausal primary osteoporosis.
• Senile form of primary osteoporosis.
• Secondary osteoporosis.
• Paget’s bone disease.
• Metastatic bone damage in malignant solid tumors and myeloma (to reduce the risk of pathological fractures, spinal cord compression, tumor-related hypercalcemia, and reduce the need for radiation therapy).

Contraindications

• hypersensitivity to zoledronic acid, other bisphosphonates or any other components that make up the drug;
• severe renal insufficiency (creatinine clearance < 30 ml / min);
• pregnancy;
• breast-feeding period;
• children and adolescents (safety and efficacy of the drug have not been established).

With caution, impaired renal function; severe hepatic insufficiency (no data on use); bronchial asthma (if patients are hypersensitive to acetylsalicylic acid).

Side effects

Adverse reactions are listed below by organ and system, with an indication of the frequency of their occurrence. Frequency criteria: very common (≥1/10), common (≥1/100, <1/10), sometimes (≥1/1,000, <1/100), rarely – (≥1/10,000, <1/1,000), very rare (

From the side of hematopoietic organs:  often-anemia, sometimes-thrombocytopenia, leukopenia; rarely-pancytopenia.

Respiratory system disorders:  sometimes-shortness of breath, cough.

From the side of the skin and skin appendages:  sometimes-itching, rash (including erymatous and macular), increased sweating.

Musculoskeletal disorders:  often-bone pain, myalgia, arthralgia, generalized pain; sometimes-muscle cramps.

From the cardiovascular system:  sometimes-a marked increase or decrease in blood pressure; rarely-bradycardia.

From the urinary system:  often-impaired renal function; sometimes-acute renal failure, hematuria, proteinuria.

From the immune system:  sometimes-hypersensitivity reactions; rarely-angioedema.

Local reactions:  pain, irritation, swelling, infiltrate formation at the injection site.

Violations of laboratory parameters:  very often – hypophosphatemia; often-increased serum creatinine and urea concentrations, hypocalcemia; sometimes-hypomagnesemia, hypokalemia; rarely-hyperkalemia, hypernatremia.

Nervous system disorders:  often-headache; sometimes-dizziness, anxiety, paresthesia, tremor, taste disorders, hypesthesia, hyperesthesia, sleep disorders; rarely-confusion.

From the side of the visual organ:  often-conjunctivitis; sometimes-blurred vision; very rarely-uveitis, episcleritis.

From the gastrointestinal tract:  often – nausea, vomiting, anorexia; sometimes-diarrhea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth.

Other services:  often-flu-like syndrome (including general malaise, chills, pain, fever), fever, sometimes-asthenia, peripheral edema; chest pain, weight gain. Patients treated with bisphosphonates, including zoledronic acid, have occasionally developed osteonecrosis of the jaw (usually after tooth extraction or other dental intervention). In very rare cases, lowering blood pressure during zoledronic acid therapy resulted in syncope or circulatory collapse.

Interaction

As solvents, do not use solutions containing calcium or any divalent cations, in particular Ringer’s lactate solution. When used concomitantly with antitumor drugs, diuretics, antibiotics, and analgesics, no clinically significant interactions were observed. Bisphosphonates and aminoglycosides have a unidirectional effect on the concentration of calcium in the blood serum, so when they are administered simultaneously, the risk of hypocalcemia and hypomagnesemia increases. Caution is recommended when using zoledronic acid concomitantly with drugs that may have a potentially nephrotoxic effect. Patients with multiple myeloma may have an increased risk of developing impaired renal function with intravenous bisphosphonates in combination with thalidomide. The drug should not be mixed with other medications.

How to take, course of use and dosage

Intravenous, drip, for at least 15 minutes.

In patients with hypercalcemia due to malignant tumors (calcium concentration with albumin correction ≥12 mg/dl or 3 mmol/L), the recommended dose of Rezoklastin FS is 4 mg, once. The infusion is carried out under the condition of adequate hydration of the patient.

For metastatic bone damage, malignant solid tumors and myeloma, the recommended dose of the drug is 4 mg every 3-4 weeks. Additionally, it is recommended to prescribe oral calcium at a dose of 500 mg/day and vitamin D at a dose of 400 IU/day.

In postmenopausal and senile forms of primary osteoporosis, in order to increase bone mineral density, prevent fractures of the vertebral bodies and other skeletal bones, the recommended dose of the drug is 5 mg, once a year.

In secondary osteoporosis, the recommended dose of Rezoklastin FS is 5 mg once a year. If the intake of calcium and vitamin D from food is insufficient, you should additionally prescribe calcium and vitamin D preparations. The duration of use of the drug is determined by the doctor individually, depending on the patient’s condition.

For the treatment of Paget’s bone disease, a single intravenous use of the drug at a dose of 5 mg is recommended. Due to the fact that Paget’s bone disease is characterized by a high level of bone metabolism, all patients with this disease are recommended to take a daily allowance of calcium and vitamin D for the first 10 days after use of zoledronic acid.

Repeated treatment with zoledronic acid of Paget’s bone disease. After the first use of the drug, a long period of remission is observed. Currently, there are no specific data on the repeated treatment of Paget’s bone disease.

However, the possibility of repeated use of the drug can be considered if a relapse of the disease is detected in patients based on the following criteria: the absence of normalization of serum ATP activity, an increase in its activity in dynamics, as well as the presence of clinical signs of Paget’s bone disease, detected during a medical examination 12 months after the first dose of zoledronic acid.

Overdose

In case of accidental overdose of the drug, the patient should be under constant medical supervision. In case of hypocalcemia accompanied by clinical manifestations, an infusion of calcium gluconate is indicated.

Special instructions

Before the infusion, the patient should be excluded from the presence of dehydration. If necessary, the use of saline solution before, in parallel or after the infusion of zoledronic acid is recommended. Hyperhydration of the patient should be avoided due to the risk of complications from the cardiovascular system.

When deciding whether to use Rezoklastin in patients with hypercalcemia due to a malignant tumor, against the background of impaired renal function, it is necessary to assess the patient’s condition and draw a conclusion about the ratio of potential benefits and possible risks of treatment. After use of the drug, constant monitoring of the concentration of calcium, magnesium, phosphorus and creatinine in the blood serum is necessary.

Renal function should be carefully monitored during zoledronic acid therapy. Risk factors for impaired renal function include dehydration, previous renal failure, repeated use of zoledronic acid or other bisphosphonates, as well as the use of nephrotoxic drugs, and too rapid use of the drug.

It should be borne in mind that when prescribing other bisphosphonates to patients with asthma sensitive to acetylsalicylic acid, cases of bronchospasm have been noted, but such cases have not yet been reported with the use of zoledronic acid.

In cancer patients treated with bisphosphonates, including zoledronic acid, cases of osteonecrosis of the jaw have been described, and therefore, before starting treatment, it is necessary to provide a dental examination and, if there are risk factors (anemia, coagulopathy, infection, poor hygiene or oral diseases, concomitant chemotherapy or radiation therapy, corticosteroid treatment), conduct appropriate preventive procedures.

During treatment with zoledronic acid, patients with risk factors should avoid dental surgery if possible. To reduce the frequency of adverse reactions after Rezoklastin FS infusion, patients should be prescribed paracetamol or ibuprofen immediately after use of the drug.

Care must be taken when driving vehicles and other mechanisms.

Form of production

Concentrate for preparation of solution for infusions.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 °C.

Shelf

life is 2 years.

Active ingredient

Zoledronic acid

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Paget’s Disease